The overarching goal of the proposed research is to understand, from a cognitive neuroscience perspective, how information about an event is successfully encoded into episodic memory. Functional magnetic resonance imaging (fMRI) will be employed to identify neural activity elicited during the successful encoding of experimental items such as words and pictures and their associations either with other items (item-item encoding), or with one or more contextual features (item-context encoding). The theoretical perspective guiding the proposed research derives from the proposals that an episodic memory is represented in terms of the processing engaged by an event as it is experienced, and that successful episodic encoding requires that the various features constituting an event are 'bound' or integrated into a cohesive memory representation. Guided by this perspective, experiments will address the roles of the cerebral cortex and the medial temporal lobe in the 'binding' of within- versus across- modality item-context and item-item associations. Other experiments will investigate the neural correlates of the formation of within- and across-modality associations between different contextual features. Another experiment will investigate the neural correlates of the formation of temporal associations between items presented at different times. In a second strand of the research, the focus will be on neural activity that appears to play a 'permissive' role in episodic encoding, rather than supporting processes engaged by a specific study task. Experiments will be conducted to elucidate i) the functional significance of the relative attenuation of neural activity elicited in some cortical regions by study items that are remembered rather than forgotten on a later memory test, and ii) modulations of pre-stimulus activity that also are predictive of later memory performance. Disabling impairments of episodic memory are prominent in several common neurological conditions, notably Alzheimer's disease and traumatic brain injury. Episodic memory dysfunction is also a significant component of several common psychiatric disorders, including schizophrenia, depression and post-traumatic stress disorder. In addition, episodic memory declines substantially and, relative to other kinds of memory, disproportionately, with increasing age. The proposed research will contribute to the detailed understanding of the neurocognitive processes that support normally-functioning episodic memory, an understanding that is necessary for the elucidation of different kinds of episodic memory disorders and the development of effective therapeutic interventions. PUBLIC HEALTH RELEVANCE: Disabling impairments of episodic memory - memory for unique events - are found in numerous neurological and psychiatric conditions. The proposed research will contribute to the detailed understanding of normally-functioning episodic memory that is necessary if different kinds of episodic memory disorders are to be fully understood and effectively treated.